Optical isomers, more commonly called enantiomers, are important in several fields, including the pharmaceutical, chemical, essential oils, flavor, and food industries. The vast majority of useful drugs contain one or several chiral centers. Obtaining high enantiomeric purity of therapeutics is essential, since it is well known that the wrong enantiomer can cause harmful side effects. Thus, both producing enantiomerically pure formulations and testing for enantiomeric purity are critical. Unfortunately, both of these activities remain significant challenges, even with the current state-of-the-art analytical instrumentation. To date no generally applicable method for high throughput enantiomeric purity screening is available to the researcher.
There are known improvements to chiral analysis techniques, more specifically, in the area of reducing noise associated with the measurement of the additional optical rotation induced by a chiral sample. Single beam methods utilizing electronic or optical means to filter noise are quite common (see, for example, WO 01/06918). Other known methods utilize dual beams either by comparison to a reference cell (U.S. Pat. No. 4,912,059), mixing out of phase sinusoidal signals (U.S. Pat. No. 5,477,327), switching between a signal and reference beam (U.S. Pat. No. 5,621,528), or using a two frequency laser source with two orthogonal linear polarized waves (U.S. Pat. Nos. 5,896,198 and 6,327,037). These methods attempt to determine the displacement from the null point of optical transmission.
It is also known to use pockels cell modulation for differential chiral analysis in flow cells (U.S. Pat. No. 5,168,326). This technology involves the application of oscillating voltage to the pockels cell to produce alternating beams of linearly polarized light and circular light. By subtracting the rotation angles calculated for both beams, common sources of noise are effectively canceled out, giving a more sensitive measurement.
Thus, there remains a need to more accurately determine the additional optical rotation introduced by a chiral sample by reducing noise associated with the measurement.